title: Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.
abstract: OBJECTIVE
  To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck.
  
  
  METHODS
  Nonrandomized, prospective trial.
  
  
  METHODS
  A comprehensive cancer center.
  
  
  METHODS
  Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity.
  
  
  METHODS
  Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy.
  
  
  RESULTS
  A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L.
  
  
  CONCLUSIONS
  Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.
authors.affiliation: Dana-Faber Cancer Institute, Boston, Massachusetts.
authors.forename: A I
authors.initials: AI
authors.lastname: Dreyfuss
authors.forename: J R
authors.initials: JR
authors.lastname: Clark
authors.forename: J E
authors.initials: JE
authors.lastname: Wright
authors.forename: C M
authors.initials: CM
authors.lastname: Norris
authors.forename: P M
authors.initials: PM
authors.lastname: Busse
authors.forename: J W
authors.initials: JW
authors.lastname: Lucarini
authors.forename: B G
authors.initials: BG
authors.lastname: Fallon
authors.forename: D
authors.initials: D
authors.lastname: Casey
authors.forename: J W
authors.initials: JW
authors.lastname: Andersen
authors.forename: R
authors.initials: R
authors.lastname: Klein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000097:blood; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013763:Tetrahydrofolates / Q000097:blood
chemical_list: D013763:Tetrahydrofolates; D002945:Cisplatin; D002955:Leucovorin; C005984:5-methyltetrahydrofolate; D005472:Fluorouracil